Even though there have been advances in pharmacotherapy for
depression beyond Selective Serotonin Reuptake Inhibitors (SSRIs), they
remain the mainstay for treatment of depression, especially since many
are now available in generic form. They are used also for a variety of
anxiety disorders, and one is indicated for bulimia nervosa and
premenstrual dysphoric disorder

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[ILLUSTRATION OMITTED]

Selective Serotonin Reuptake Inhibitors (SSRIs) have been on the
market since 1987 (when fluoxetine was introduced) and have subsequently
dominated market share. They have largely replaced tricyclic
antidepressants and monoamine oxidase inhibitors due to their favorable
side effect profile and their ease of titration to therapeutic doses,
not to mention escaping the lethality of tricyclics in overdose. SSRIs
are thought to work by blocking reuptake ofserotonin. They appear to
function at low doses, which frequently turn out to be their therapeutic
doses--a huge advantage over their predecessors. Most clinicians believe
that the members of the SSRI class are equally effective in large
populations, yet responses may vary considerably with each medication in
individual patients. One misconception is that these medications are
more effective than their predecessors, which is not true. Rather, they
tend to be utilized more because of the advantages just mentioned.
Interestingly, some researchers and clinicians have noted that
tricyclics and MAOI drugs may be more effective in severe depression
than the SSRI class. In general, new antidepressant research has moved
on to compounds with other mechanisms of action.

As a group, SSRIs are most often used to treat depression but some
members of the family have other indications including post traumatic
stress disorder, generalized anxiety disorder, social anxiety disorder,
obsessive compulsive disorder, and panic disorder, as well as bulimia
nervosa and premenstrual dysphoric disorder.

SSRIs are contraindicated when patients are on MAOI medications and
a two-week washout period is required from the MAOI to an SSRI. When one
goes from the SSRI to a MAOI, the same two-week washout period applies
except with fluoxetine, where five weeks are required. SSRIs should not
be combined with some older antipsychotics, including pimozide and
thioridazine. Combining SSRIs with tricyclic antidepressants may be done
but only cautiously and under close supervision by an expert prescriber.
The SSRI can cause an increase in the serum level of the tricyclic
antidepressant and can cause delirium and toxicity. Generally speaking,
SSRIs and other antidepressants should not be used in bipolar disorder
or psychotic disorders, at least without accompanying mood stabilizers
or antipsychotics. The worry here is that they may cause a manic
"switch." The prescribing physician, as well as all other
physicians working with the patient, should know about each and every
other medication the patient is taking, whether prescription or
over-the-counter. There are some drug-drug reactions that occur with
SSRIs and other non-psychiatric medications, and some of these effects
are limited to specific SSRIs. The prescriber should be aware of these
issues. One SSRI should not be combined with another or with any other
serotonergic medications unless cross-tapering for fear of the
development of serotonin syndrome, which can be life-threatening. This
syndrome could also occur as a result of combining SSRIs with the
over-the-counter entity known as St. John's Wort.

When SSRI medications are weaned (abruptly in particular), there
are well-documented reports of discontinuation syndrome, which can
involve flu-like symptoms and/or a rapid, intense exacerbation of mood
and anxiety symptoms even to the point of suicidal ideation. This may
occur less with fluoxetine due to the lengthy half-life of the active
compound and its metabolite. Incidentally, there are no dietary
restrictions with SSRI medications. Any deaths with SSRI overdoses
usually involve combining the drug with other drugs or alcohol. There
were reports in the 1980s associating SSRIs with homicidal rage and
suicide; further studies have not borne this out. Recently, however,
concerns have been raised about an increase in suicidal behavior or
impulses in adolescents on these medications. The risk appears greatest
in the early stages of treatment. All patients should be monitored
closely, but especially at the beginning few weeks of treatment. This
being said, when depressed patients are treated effectively, the suicide
rate drops accordingly.

A rule of thumb about dosing these medications is that with anxiety
disorders, one generally starts with lower dosages and gradually works
upward, even more slowly than with depression. Additionally, certain
disorders, including obsessive compulsive disorder and bulimia nervosa,
may require the highest doses indicated for longer periods of time than
for depression to see results.

Side effects of SSRIs are generally milder than with other
antidepressants, which increase their tolerability and patient
compliance. Approximately three-fourths of patients do not experience
significant side effects at the starting doses of SSRIs. If patients do
experience side effects, they are usually time-limited to around two
weeks. However, there are some patients that cannot tolerate these
medications at all and do not show increased ability to tolerate them as
time goes on. The most common side effects include gastrointestinal
distress, sexual dysfunction, and anxiety. Other more rare effects can
include insomnia, sedation, electrolyte disturbances, allergies,
endocrine problems, and serotonin syndrome, which can be quite serious
and even fatal. Gastrointestinal bleeding can be associated with SSRIs,
especially if they are combined with non-steroidal anti-inflammatory
drugs. Again, with rare exceptions, the side effects with these
medications are generally more limited than with other alternatives.

There are differences of opinion about numbers of trials of SSPds,
but most practitioners would probably choose a medication with a
different mechanism of action after trials of two different SSRIs with
adequate time at an adequate dosage. Certainly other alternatives exist,
and new forms of treatment for depression are continually being
developed, including some treatments that do not involve taking
medications. These options of course have their advantages and
disadvantages and will be explored in future articles.

An additional consideration is that a minority of patients report a
loss of efficacy of their SSRI months or years after its introduction.
This is not fully understood, but various remedies have been attempted,
including increasing the dose, switching to another medication either in
the SSRI class or outside of it, or augmenting with another agent. It is
safe to say that SSRIs have revolutionized the treatment of depression
and some other psychiatric disorders and have resulted in more people
being adequately treated. Also, more patients have remained compliant
with their treatment due to the better side-effect profile. As more and
more medications of this class become available as generics, cost is
less of an issue. While not a panacea, with appropriate caution taken
about patients' medical conditions and other medications, SSRIs
continue to be a mainstay of treatment for depression and anxiety and to
relieve a lot of suffering.

This article is approved by the following for continuing education
credit:

The American Psychotherapy Association provides this continuing
education credit for Diplomates and certified members, whom we recommend
obtain 15 CEs per year to maintain their status.

After studying this article, participants should be better able to
do the following:

1. Review the many uses for the Selective Serotonin Reupatke
Inhibitors

2. Illustrate the drawbacks or possible side effects of Selective
Serotonin Reuptake Inhibitors

To earn CE credit, complete the exam for this article on page 47 or
complete the exam online at www.americanpsychotherapy.com (select
"Online CE").

Dr. David Diaz is a graduate of the Indiana University School of
Medicine and its residency program in psychiatry and has been in
practice 20 years. He is currently the medical director of an adult
psychiatry unit at Larue D. Carter Memorial Hospital in Indianapolis and
is active in the teaching of medical students and residents. He can be
reached at drdiaz@iupui.edu.

Dr. Maria Poor is a graduate of the Indiana University School of
Medicine and its psychiatry residency program. She has been in practice
in Indianapolis for 20 years. She is currently the medical director of
an adult psychiatry unit at Larue D. Carter Memorial Hospital * in
Indianapolis. She is active in the teaching of medical students and
residents and has won recognition for her efforts. She can be contacted
at mpoor@iupui.edu.